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Effects of felbamate on the pharmacokinetics of phenobarbital
Author(s) -
Reidenberg Pascale,
Glue Paul,
Banfield Christopher R.,
Colucci Robert D.,
Meehan Jeffrey W.,
Radwanski Elaine,
Mojavarian Parviz,
Lin ChinChung,
Nezamis James,
Guillaume Michel,
Affrime Melton B.
Publication year - 1995
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/0009-9236(95)90244-9
Subject(s) - felbamate , phenobarbital , pharmacokinetics , pharmacology , anticonvulsant , chemistry , mephenytoin , drug interaction , placebo , medicine , cytochrome p450 , cyp2c19 , metabolism , biochemistry , epilepsy , alternative medicine , pathology , psychiatry
The effects of felbamate on the pharmacokinetics of phenobarbital and one of its main metabolites, parahydroxyphenobarbital, were assessed in a parallel‐group, placebo‐controlled, double‐blind study, in 24 healthy volunteers. Pharmacokinetic parameters of phenobarbital and parahydroxyphenobarbital were determined from plasma and urine samples obtained after 28 days of daily administration of 100 mg phenobarbital and after a further 9 days of phenobarbital plus 2400 mg/day felbamate or placebo. Felbamate increased phenobarbital values for area under the plasma concentration‐time curve from 0 to 24 hours and maximum concentration by 22% and 24%, respectively, whereas placebo had no effect. This increase was caused by a reduction in parahydroxylation of phenobarbital and possibly through effects on other metabolic pathways. Because felbamate inhibits the S ‐mephenytoin hydroxylase (CYP2C19) isozyme in vitro, it appears that phenobarbital hydroxylation is mediated in part by this isozyme. Clinical Pharmacology & Therapeutics (1995) 58 , 279–287; doi: